In the 1970s use of radioactively labeled benzodiazepine derivatives allowed the detection of specific nanomolar benzodiazepine receptor sites in brain membrane (15-17). These sites have a very high affinity for the benzodiaz-epines, binding in low (nanomolar) concentration ranges. Binding to these receptors is reversible, saturable, and stereospecific. Nanomolar benzodiazepine receptors have now been identified in human brain, where they are widely distributed. The specific membrane protein that accounts for the majority of nanomolar benzodiaz-epine binding has a molecular weight of approximately 50,000 daltons and has been purified from animal and human brain (18).
High-affinity benzodiazepine binding has also been observed in peripheral, nonneuronal tissue (19). A different class of benzodiazepine receptor molecules causes this binding, because both the potency and the tissue distribution of this binding are different from that at the central-type receptor. This second class of high-affinity benzodiazepine binding sites was designated "peripheral type receptor'' (19), but it was subsequently shown that the peripheral-type benzodiazepine receptor is also present in neuronal tissue. Thus, both peripheral and central high-affinity benzodiazepine receptors exist in the brain.
High nanomolar and low micromolar benzodiaz-epine binding sites have been identified more recently in brain membranes (20, 21). In addition, another ben-zodiazepine receptor that binds in the high nanomolar range has been identified in brain cytosol (21). These novel benzodiazepine-binding sites are stereospecific and have potencies for benzodiazepine binding that correlate with the ability of these compounds to inhibit maximal electric shock-induced seizures. Benzodiazepine bound to micromolar benzodiazepine receptors is displaced by phenytoin. These results indicate that high nanomolar and low-micromolar-affinity benzodiazepine receptors may represent important anticonvulsant binding sites in brain membrane that mediate some of the effects of benzodiazepines in high concentration in curtailing status epilepticus, generalized tonic-clonic seizures, and maximal electric shock-induced seizures.
Benzodiazepines are effective in nanomolar concentrations in blocking pentylenetetrazol-induced seizures in animals and in treating absence seizures. In addition, benzodiazepines in high nanomolar and low micromolar ranges inhibit maximal electric shock-induced seizures in animals. Furthermore, benzodiazepines are effective in humans in stopping generalized tonic-clonic seizures and status epilepticus when given in intravenous doses that produce low micromolar serum concentrations. The potency of the benzodiazepines in blocking maximal electric shock-induced seizures, however, correlates in neither time nor consequence with their ability to inhibit pentylenetetrazol-induced seizures or bind to the nanomolar central benzodiazepine receptor (20). Thus, other mechanisms appear to underlie this generalized anticonvulsant property of the benzodiazepines in high concentration ranges. Lower-affinity benzodiazepine binding sites in the high nanomolar and low micromolar ranges have also been described (20, 22). These lower-affinity receptor sites come into play in the concentration ranges in which benzodiazepines produce effects on maximal electric shock-induced seizures in animals, on generalized tonic-clonic seizures in man, and on SRF in cultured neurons.
Diazepam and clonazepam reduce SRF in high nanomolar and low micromolar concentrations (7). These concentrations are above therapeutic free-serum concentrations achieved in ambulatory patients treated with benzodiazepines but are within the ranges of freeserum concentrations achieved in patients treated for status epilepticus or acutely for generalized tonic-clonic seizures. In addition to the discrepancy in concentration ranges, the potency of benzodiazepines for suppressing SRF does not correlate with benzodiazepine binding to the nanomolar central receptor or with their ability to inhibit pentylenetetrazol-induced seizures but does correlate with binding to the lower-affinity benzodiazepine binding system.
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With all the stresses and strains of modern living, panic attacks are become a common problem for many people. Panic attacks occur when the pressure we are living under starts to creep up and overwhelm us. Often it's a result of running on the treadmill of life and forgetting to watch the signs and symptoms of the effects of excessive stress on our bodies. Thankfully panic attacks are very treatable. Often it is just a matter of learning to recognize the symptoms and learn simple but effective techniques that help you release yourself from the crippling effects a panic attack can bring.